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Q99988

- GDF15_HUMAN

UniProt

Q99988 - GDF15_HUMAN

Protein

Growth/differentiation factor 15

Gene

GDF15

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 126 (01 Oct 2014)
      Sequence version 3 (30 Nov 2010)
      Previous versions | rss
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    Functioni

    GO - Molecular functioni

    1. cytokine activity Source: ProtInc

    GO - Biological processi

    1. cell-cell signaling Source: ProtInc
    2. signal transduction Source: ProtInc
    3. transforming growth factor beta receptor signaling pathway Source: ProtInc

    Keywords - Molecular functioni

    Cytokine, Growth factor

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Growth/differentiation factor 15
    Short name:
    GDF-15
    Alternative name(s):
    Macrophage inhibitory cytokine 1
    Short name:
    MIC-1
    NSAID-activated gene 1 protein
    Short name:
    NAG-1
    NSAID-regulated gene 1 protein
    Short name:
    NRG-1
    Placental TGF-beta
    Placental bone morphogenetic protein
    Prostate differentiation factor
    Gene namesi
    Name:GDF15
    Synonyms:MIC1, PDF, PLAB, PTGFB
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    ProteomesiUP000005640: Chromosome 19

    Organism-specific databases

    HGNCiHGNC:30142. GDF15.

    Subcellular locationi

    Secreted Curated

    GO - Cellular componenti

    1. extracellular region Source: ProtInc
    2. extracellular space Source: UniProtKB-KW
    3. extracellular vesicular exosome Source: UniProt

    Keywords - Cellular componenti

    Secreted

    Pathology & Biotechi

    Organism-specific databases

    PharmGKBiPA134866647.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Signal peptidei1 – 2929Sequence AnalysisAdd
    BLAST
    Propeptidei30 – 194165Sequence AnalysisPRO_0000033992Add
    BLAST
    Chaini195 – 308114Growth/differentiation factor 15PRO_0000033993Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Glycosylationi70 – 701N-linked (GlcNAc...)Sequence Analysis
    Disulfide bondi211 ↔ 274By similarity
    Disulfide bondi240 ↔ 305By similarity
    Disulfide bondi244 ↔ 307By similarity
    Disulfide bondi273 – 273InterchainBy similarity

    Keywords - PTMi

    Cleavage on pair of basic residues, Disulfide bond, Glycoprotein

    Proteomic databases

    MaxQBiQ99988.
    PaxDbiQ99988.
    PeptideAtlasiQ99988.
    PRIDEiQ99988.

    PTM databases

    PhosphoSiteiQ99988.

    Miscellaneous databases

    PMAP-CutDBQ9BWA0.

    Expressioni

    Tissue specificityi

    Highly expressed in placenta, with lower levels in prostate and colon and some expression in kidney.

    Gene expression databases

    BgeeiQ99988.
    CleanExiHS_GDF15.
    GenevestigatoriQ99988.

    Organism-specific databases

    HPAiCAB062554.
    HPA011191.

    Interactioni

    Subunit structurei

    Homodimer; disulfide-linked.By similarity

    Protein-protein interaction databases

    BioGridi114895. 4 interactions.
    IntActiQ99988. 2 interactions.
    STRINGi9606.ENSP00000252809.

    Structurei

    3D structure databases

    ProteinModelPortaliQ99988.
    SMRiQ99988. Positions 209-307.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Sequence similaritiesi

    Belongs to the TGF-beta family.Curated

    Keywords - Domaini

    Signal

    Phylogenomic databases

    eggNOGiNOG235805.
    HOGENOMiHOG000143379.
    HOVERGENiHBG051718.
    InParanoidiQ99988.
    KOiK05504.
    OMAiSWDVTRP.
    PhylomeDBiQ99988.
    TreeFamiTF351787.

    Family and domain databases

    Gene3Di2.10.90.10. 1 hit.
    InterProiIPR029034. Cystine-knot_cytokine.
    IPR001839. TGF-b_C.
    IPR015615. TGF-beta-rel.
    [Graphical view]
    PANTHERiPTHR11848. PTHR11848. 1 hit.
    PfamiPF00019. TGF_beta. 1 hit.
    [Graphical view]
    SMARTiSM00204. TGFB. 1 hit.
    [Graphical view]
    SUPFAMiSSF57501. SSF57501. 1 hit.
    PROSITEiPS51362. TGF_BETA_2. 1 hit.
    [Graphical view]

    Sequencei

    Sequence statusi: Complete.

    Sequence processingi: The displayed sequence is further processed into a mature form.

    Q99988-1 [UniParc]FASTAAdd to Basket

    « Hide

    MPGQELRTVN GSQMLLVLLV LSWLPHGGAL SLAEASRASF PGPSELHSED    50
    SRFRELRKRY EDLLTRLRAN QSWEDSNTDL VPAPAVRILT PEVRLGSGGH 100
    LHLRISRAAL PEGLPEASRL HRALFRLSPT ASRSWDVTRP LRRQLSLARP 150
    QAPALHLRLS PPPSQSDQLL AESSSARPQL ELHLRPQAAR GRRRARARNG 200
    DHCPLGPGRC CRLHTVRASL EDLGWADWVL SPREVQVTMC IGACPSQFRA 250
    ANMHAQIKTS LHRLKPDTVP APCCVPASYN PMVLIQKTDT GVSLQTYDDL 300
    LAKDCHCI 308
    Length:308
    Mass (Da):34,140
    Last modified:November 30, 2010 - v3
    Checksum:i2FF3959021B95238
    GO

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti269 – 2691V → E in AAB88913. (PubMed:9375789)Curated
    Sequence conflicti288 – 2881T → A in AAF89834. (PubMed:9426002)Curated

    Natural variant

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti9 – 91V → L.4 Publications
    Corresponds to variant rs1059519 [ dbSNP | Ensembl ].
    VAR_047646
    Natural varianti48 – 481S → T.3 Publications
    Corresponds to variant rs1059369 [ dbSNP | Ensembl ].
    VAR_010386
    Natural varianti202 – 2021H → D.1 Publication
    Corresponds to variant rs1058587 [ dbSNP | Ensembl ].
    VAR_047647

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    U88323 mRNA. Translation: AAB88913.1.
    AB000584 mRNA. Translation: BAA19151.1.
    AF019770 mRNA. Translation: AAB88673.1.
    AF003934 mRNA. Translation: AAC24456.1.
    AK291530 mRNA. Translation: BAF84219.1.
    BT019465 mRNA. Translation: AAV38272.1.
    AC008397 Genomic DNA. No translation available.
    CH471106 Genomic DNA. Translation: EAW84694.1.
    BC000529 mRNA. Translation: AAH00529.1.
    BC008962 mRNA. Translation: AAH08962.1.
    AF008303 Genomic DNA. Translation: AAC39537.1.
    AF173860 mRNA. Translation: AAF89834.1.
    CCDSiCCDS12376.1.
    PIRiJC5697.
    RefSeqiNP_004855.2. NM_004864.2.
    UniGeneiHs.616962.

    Genome annotation databases

    EnsembliENST00000252809; ENSP00000252809; ENSG00000130513.
    GeneIDi9518.
    KEGGihsa:9518.
    UCSCiuc002niv.2. human.

    Polymorphism databases

    DMDMi313104195.

    Keywords - Coding sequence diversityi

    Polymorphism

    Cross-referencesi

    Web resourcesi

    Atlas of Genetics and Cytogenetics in Oncology and Haematology

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    U88323 mRNA. Translation: AAB88913.1 .
    AB000584 mRNA. Translation: BAA19151.1 .
    AF019770 mRNA. Translation: AAB88673.1 .
    AF003934 mRNA. Translation: AAC24456.1 .
    AK291530 mRNA. Translation: BAF84219.1 .
    BT019465 mRNA. Translation: AAV38272.1 .
    AC008397 Genomic DNA. No translation available.
    CH471106 Genomic DNA. Translation: EAW84694.1 .
    BC000529 mRNA. Translation: AAH00529.1 .
    BC008962 mRNA. Translation: AAH08962.1 .
    AF008303 Genomic DNA. Translation: AAC39537.1 .
    AF173860 mRNA. Translation: AAF89834.1 .
    CCDSi CCDS12376.1.
    PIRi JC5697.
    RefSeqi NP_004855.2. NM_004864.2.
    UniGenei Hs.616962.

    3D structure databases

    ProteinModelPortali Q99988.
    SMRi Q99988. Positions 209-307.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 114895. 4 interactions.
    IntActi Q99988. 2 interactions.
    STRINGi 9606.ENSP00000252809.

    PTM databases

    PhosphoSitei Q99988.

    Polymorphism databases

    DMDMi 313104195.

    Proteomic databases

    MaxQBi Q99988.
    PaxDbi Q99988.
    PeptideAtlasi Q99988.
    PRIDEi Q99988.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENST00000252809 ; ENSP00000252809 ; ENSG00000130513 .
    GeneIDi 9518.
    KEGGi hsa:9518.
    UCSCi uc002niv.2. human.

    Organism-specific databases

    CTDi 9518.
    GeneCardsi GC19P018496.
    H-InvDB HIX0014912.
    HGNCi HGNC:30142. GDF15.
    HPAi CAB062554.
    HPA011191.
    MIMi 605312. gene.
    neXtProti NX_Q99988.
    PharmGKBi PA134866647.
    GenAtlasi Search...

    Phylogenomic databases

    eggNOGi NOG235805.
    HOGENOMi HOG000143379.
    HOVERGENi HBG051718.
    InParanoidi Q99988.
    KOi K05504.
    OMAi SWDVTRP.
    PhylomeDBi Q99988.
    TreeFami TF351787.

    Miscellaneous databases

    ChiTaRSi GDF15. human.
    GeneWikii GDF15.
    GenomeRNAii 9518.
    NextBioi 35670.
    PMAP-CutDB Q9BWA0.
    PROi Q99988.
    SOURCEi Search...

    Gene expression databases

    Bgeei Q99988.
    CleanExi HS_GDF15.
    Genevestigatori Q99988.

    Family and domain databases

    Gene3Di 2.10.90.10. 1 hit.
    InterProi IPR029034. Cystine-knot_cytokine.
    IPR001839. TGF-b_C.
    IPR015615. TGF-beta-rel.
    [Graphical view ]
    PANTHERi PTHR11848. PTHR11848. 1 hit.
    Pfami PF00019. TGF_beta. 1 hit.
    [Graphical view ]
    SMARTi SM00204. TGFB. 1 hit.
    [Graphical view ]
    SUPFAMi SSF57501. SSF57501. 1 hit.
    PROSITEi PS51362. TGF_BETA_2. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    1. "PLAB, a novel placental bone morphogenetic protein."
      Hromas R., Hufford M., Sutton J., Xu D., Li Y., Lu L.
      Biochim. Biophys. Acta 1354:40-44(1997) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANT ASP-202.
      Tissue: Placenta.
    2. "Human cDNA encoding a novel TGF-beta superfamily protein highly expressed in placenta."
      Yokoyama-Kobayashi M., Saeki M., Sekine S., Kato S.
      J. Biochem. 122:622-626(1997) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANTS LEU-9 AND THR-48.
      Tissue: Fibrosarcoma.
    3. Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANTS LEU-9 AND THR-48.
    4. "Cloning and characterization of a novel member of the transforming growth factor-beta/bone morphogenetic protein family."
      Paralkar V.M., Vail A.L., Grasser W.A., Brown T.A., Xu H., Vukicevic S., Ke H.Z., Qi H., Owen T.A., Thompson D.D.
      J. Biol. Chem. 273:13760-13767(1998) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANT LEU-9.
      Tissue: Placenta.
    5. "Cloning of human full-length CDSs in BD Creator(TM) system donor vector."
      Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., Phelan M., Farmer A.
      Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANTS LEU-9 AND THR-48.
    6. "Complete sequencing and characterization of 21,243 full-length human cDNAs."
      Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.
      , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
      Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
      Tissue: Placenta.
    7. "The DNA sequence and biology of human chromosome 19."
      Grimwood J., Gordon L.A., Olsen A.S., Terry A., Schmutz J., Lamerdin J.E., Hellsten U., Goodstein D., Couronne O., Tran-Gyamfi M., Aerts A., Altherr M., Ashworth L., Bajorek E., Black S., Branscomb E., Caenepeel S., Carrano A.V.
      , Caoile C., Chan Y.M., Christensen M., Cleland C.A., Copeland A., Dalin E., Dehal P., Denys M., Detter J.C., Escobar J., Flowers D., Fotopulos D., Garcia C., Georgescu A.M., Glavina T., Gomez M., Gonzales E., Groza M., Hammon N., Hawkins T., Haydu L., Ho I., Huang W., Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., Larionov V., Leem S.-H., Lopez F., Lou Y., Lowry S., Malfatti S., Martinez D., McCready P.M., Medina C., Morgan J., Nelson K., Nolan M., Ovcharenko I., Pitluck S., Pollard M., Popkie A.P., Predki P., Quan G., Ramirez L., Rash S., Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A., She X., Smith D., Slezak T., Solovyev V., Thayer N., Tice H., Tsai M., Ustaszewska A., Vo N., Wagner M., Wheeler J., Wu K., Xie G., Yang J., Dubchak I., Furey T.S., DeJong P., Dickson M., Gordon D., Eichler E.E., Pennacchio L.A., Richardson P., Stubbs L., Rokhsar D.S., Myers R.M., Rubin E.M., Lucas S.M.
      Nature 428:529-535(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    8. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    9. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
      The MGC Project Team
      Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
      Tissue: Muscle.
    10. "Identification of a novel member of the TGF-beta superfamily highly expressed in human placenta."
      Lawton L.N., de Fatima Bonaldo M., Jelenc P.C., Qiu L., Baumes S.A., Marcelino R.A., de Jesus G.M., Wellington S., Knowles J.A., Warburton D., Brown S., Soares M.B.
      Gene 203:17-26(1997) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 14-308.
    11. "Cyclooxygenase inhibitors regulate the expression of a TGF-beta superfamily member that has proapoptotic and antitumorigenic activities."
      Baek S.J., Kim K.S., Nixon J.B., Wilson L.C., Eling T.E.
      Mol. Pharmacol. 59:901-908(2001) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 264-308.

    Entry informationi

    Entry nameiGDF15_HUMAN
    AccessioniPrimary (citable) accession number: Q99988
    Secondary accession number(s): O14629
    , P78360, Q9BWA0, Q9NRT0
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: February 21, 2001
    Last sequence update: November 30, 2010
    Last modified: October 1, 2014
    This is version 126 of the entry and version 3 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program
    DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

    Miscellaneousi

    Keywords - Technical termi

    Complete proteome, Reference proteome

    Documents

    1. Human chromosome 19
      Human chromosome 19: entries, gene names and cross-references to MIM
    2. Human entries with polymorphisms or disease mutations
      List of human entries with polymorphisms or disease mutations
    3. Human polymorphisms and disease mutations
      Index of human polymorphisms and disease mutations
    4. MIM cross-references
      Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
    5. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3